Two Molecular Pharmacologists Create Drugs the Natural Way

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Two Molecular Pharmacologists Create Drugs the Natural Way

Mother nature can make drugs and other complicated molecules without using any toxic chemicals. Professors Bradley Moore of the University of California at San Diego and Christopher Walsh of Harvard Medical School have figured out how to do it too.

Rather than using the somewhat barbaric methods of organic chemistry, Moore and Walsh's research groups stripped down the natural process for producing complicated chemicals. They identified each molecule that living cells use to make sophisticated compounds, and then used them to produce the products they wanted.

Moore made an antibacterial agent while Walsh produced a tumor-fighting chemical, both of which appear in the August 12 online issue of Nature Chemical Biology.

Organic chemists are often stuck with the task of making drugs. When it becomes clear that a natural chemical can act as a powerful medicine, a team of them will try to mass-produce that chemical in the lab. Often, they work like dogs for months or years to develop a somewhat inefficient method for large-scale production of the drug. The process may have a dozen laborious steps and require gallons of toxic chemicals.

The research uses a method that may only require a few steps and takes place in a buffer – which is essentially pH balanced salt water.

Complicated chemicals are created from simple building blocks by a series of enzymes. Enzymes are proteins that facilitate chemical reactions. They are the workhorses of all cellular life. Moore and Walsh each made large, complicated molecules by combining the right building blocks with the proper enzymes.

Although this could make drug manufacturing a lot cleaner and more efficient, it won't soon send many organic chemists to the unemployment office. Once organic chemists have learned how to make a chemical, they can usually make thousands of variations on it and test each of them for therapeutic effects. Medicinal chemists call this SAR or structure-activity relationship testing. It would be hard to do that trick with enzymes.

Using enzymes to produce chemicals on a large scale is tricky. Many of them are very delicate. If not kept in the right liquid at a comfortable temperature, they stop working. At Berkeley, Professor Douglas Clark is developing clever ways to stabilize the protein machines so that they can be more useful as industrial catalysts.

To make a chemical the natural way, biologists must first learn how cells do it. That's not easy, but new gene sequencing and computational biology tools are making it a whole lot easier. Eventually, this may become a fantastic area for entrepreneurship. Imagine a startup company made up of three biochemists and a lawyer approaching a massive pharmaceutical company with a method to produce their blockbuster cancer drug in one step without any toxic byproducts.